Infectious bursal disease (IBD), or Gumboro Diesease, is an acute course viral disease mainly affecting broiler chickens during the growth stage. This highly contagious disease was first disclosed by Cosgrove in 1962 in the U.S. city of Gumboro (Del.). Currently, this disease is spread worldwide, and the IBD outbreak rate has increased, with a high massive mortality rate (50–75%) caused by highly virulent strains of the virus.
The disease is caused by the infectious bursal disease virus (IBDV), which has a very noticeable tropism of the lymphoid cells located in the bursa of Fabricius, causing a selective elimination of lymphocyte B precursors and, accordingly, the establishment of a severe immunosuppression. Therefore, infection by IBDV causes high massive mortality rates for two reasons: i) the actual infective cycle of IBDV, and ii) opportunistic infections of other pathogens affecting the immunodepressed animals. The immunosuppressive effect of IBDV also reduces the response of the animals to vaccines against other avian pathogens.
The economic importance of this disease is fundamentally based on these two aspects: on one hand, the high mortality rate caused by some IBDV strains in 3-week old chickens, and even older, and on the other hand, the second clinical manifestation of the disease consisting of a prolonged immunosuppression of the birds infected at early ages. The main sequelae associated to said immunosuppression are: dermatitis gangrenosa, anemia-hepatitis syndrome with inclusion bodies, E. coli infections and failures in the efficacy of other vaccinations, such as the vaccinations against the Newcastle disease and infectious bronchitis.
IBDV virions are extraordinarily resistant to environmental conditions and persist in the environment for a period of at least 4 months. The virus is transmitted through water, food or excrement, but there is no vertical transmission through the egg, nor are there chronic carriers of the disease. Therefore, success in controlling Gumboro disease is based on the application of strict hygiene and disinfection programs in the facilities, together with the preventive vaccination of reproducers and progeny. Immunization of reproductive birds has a special importance in the transmission of passive immunity to the progeny; however, the presence of said passive immunity can interfere in the efficacy of the vaccination of the progeny.
IBDV is the prototype of the genus Avibimavirus of the Birnaviridae family, a double-stranded RNA (dsRNA) virus. IBDV virions have a size of 60–65 nm, they are not enveloped and have icosahedral symmetry. The viral capsid, formed by a single layer of an average thickness of 9 nm, is constituted of two proteins: VP2 (40 kDa) and VP3 (32 kDa), which are assembled to form a non-spherical T=13 capsid. The genome of the virus is constituted of two double-stranded RNA segments of 3,129 bp (segment A) and 2,759 bp (B), respectively. Segment A contains two Open Reading Frames (ORF) called A1 and A2. ORF A1 encodes a 106 kDa protein with autoproteolytic capability. Processing of the protein gives way to three mature protean products: VP2 and VP3, which form the viral capsids, and VP4, a non-structural protein with proteolytic activity. ORF A2 encodes for a non-structural 16.5 kDa protein (VP5), the activity of which is unknown. Segment B encodes a single, 90 kDa protein, VP 1, with RNA-dependent RNA polymerase activity, which is found in purified virions associated to the ends of both viral genome fragments.
Segment A encodes for a precursor polyprotein in the 5′-VPX-VP4-VP3-3′ order. The precursor polyprotein is processed through different proteolytic processes to produce the definitive mature viral proteins, VP2 and VP3, structural components of the IBDV virion, and VP4, the viral protease responsible for processing the precursor polyprotein. It is known that during viral infection, VP2 is initially synthesized as a precursor (VPX), the C-terminus end of which is processed by proteolysis to the mature form during capsid assembly, but the exact cutting points and the proteins involved in said processing are unknown. This processing is essential in the capsid assembly process. VP2 contains the antigenic regions responsible for the induction of neutralizing antibodies, serotype and strain specificity, whereas VP3 is considered the group-specific antigen.
The serological response to the virus is mainly focused on the proteins of the capsid, VP2 and VP3. The VP3 protein is immunodominant, being invariably recognized by sera of convalescent chickens and hyperimmune animals. However, the majority of the monoclonal antibodies capable of neutralizing infectiveness of the virus recognize conformational epitopes in the VP2 protein.
Several vaccines have been disclosed which contain attenuated live IBDV (U.S. Pat. No. 5,632,989), as well as vaccines with inactivated IBDV, as well as recombinant subunit vaccines containing the IBDV VP2 protein, expressed in several systems, for example, bacteria, yeasts, viruses, etc., normally in the form of a fusion protein (U.S. Pat. No. 5,605,792 and U.S. Pat. No. 5,605,827). The possibility that VP2 forms empty chimeric capsids in combination with all or part of IBDV VP3 (U.S. Pat. No. 5,788,970, Hu et al., 1999; Wang et al., 2000; Martínez-Torrecuadrada et al., 2000a; Martínez-Torrecuadrada et al., 2000b; Cheng et al., 2001) is also known.